2017
Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity
Cao J, Peng J, An H, He Q, Boronina T, Guo S, White M, Cole P, He L. Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity. Nature Communications 2017, 8: 131. PMID: 28743992, PMCID: PMC5526866, DOI: 10.1038/s41467-017-00163-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorE1A-Associated p300 ProteinEndoplasmic Reticulum StressEndotoxemiaGene Expression ProfilingImmunoblottingInsulinInsulin ResistanceLipopolysaccharidesLiverMaleMembrane ProteinsMice, Inbred C57BLMice, ObeseObesityProtein Serine-Threonine KinasesReceptor, InsulinSignal TransductionX-Box Binding Protein 1ConceptsInsulin resistanceP300 acetyltransferase activityHigh-fat diet-fedChronic low-grade inflammationObese ob/ob miceOb/ob miceLow-grade inflammationDiet-induced obesityAcetyltransferase activityElevated plasma concentrationsPromising therapeutic targetCytoplasm of hepatocytesEndoplasmic reticulum stressObese patientsObese miceInsulin sensitivityIntestinal permeabilityOb micePlasma concentrationsDisrupts insulinTherapeutic targetImpairs insulinPharmacological inhibitionGlucose productionObesity
2005
Exendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*
Park S, Dong X, Fisher T, Dunn S, Omer A, Weir G, White M. Exendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*. Journal Of Biological Chemistry 2005, 281: 1159-1168. PMID: 16272563, DOI: 10.1074/jbc.m508307200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCell LineCell SurvivalCyclic AMPDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelExenatideGenotypeGlucagon-Like Peptide-1 ReceptorGlucoseGuinea PigsHumansHyperglycemiaImmunoblottingImmunohistochemistryImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin SecretionInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicModels, BiologicalModels, ChemicalPancreasPeptidesPhosphoproteinsPhosphorylationReceptor, InsulinReceptors, GlucagonReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTime FactorsVenomsConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsReceptor agonistExendin-4Beta cellsProgressive beta cell lossShort-term therapeutic effectsInsulin-like growth factorBeta-cell lossProgression of diabetesBeta-cell massBeta-cell replicationBeta-cell growthPancreatic β-cell growthΒ-cell growthIrs2 branchPrevents diabetesInsulin/insulin-like growth factorCell growthInsulin secretionTherapeutic effectIRS2 expressionLong-term effectsFatal diabetesCell lossInsulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*
Sadagurski M, Weingarten G, Rhodes C, White M, Wertheimer E. Insulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*. Journal Of Biological Chemistry 2005, 280: 14536-14544. PMID: 15705592, DOI: 10.1074/jbc.m410227200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBiological TransportDeoxyglucoseEpidermisFibroblastsGenotypeGlucoseHomozygoteImmunoblottingImmunoprecipitationInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsKeratinocytesMiceMice, KnockoutPhosphatidylinositol 3-KinasesPhosphoproteinsSkinThymidineTime FactorsConceptsIRS-2Glucose transportInsulin receptor substrate-2 proteinInsulin-induced glucose transportInsulin receptor substrate 2Insulin-stimulated glucose transportIRS-1 proteinCell specific associationIRS-2 proteinClassical insulin target tissuesCell-specific mannerSkin epidermal keratinocytesIRS-PICell-specific rolePositive regulatorInsulin target tissuesCell physiologyDermal fibroblastsKO cellsEpidermal keratinocytesAkt activationPhosphatidylinositolSubstrate 2Insulin receptorProtein
2002
Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL*
Wurster A, Rodgers V, White M, Rothstein T, Grusby M. Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL*. Journal Of Biological Chemistry 2002, 277: 27169-27175. PMID: 12023955, DOI: 10.1074/jbc.m201207200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-X ProteinBlotting, NorthernB-LymphocytesCell DeathCells, CulturedImmunoblottingInterleukin-4LuciferasesLymphocytesMicePromoter Regions, GeneticPropidiumProtein BindingProto-Oncogene Proteins c-bcl-2RetroviridaeSignal TransductionSTAT6 Transcription FactorTime FactorsTrans-ActivatorsTranscription, GeneticTransfectionUp-RegulationConceptsFas-induced cell deathIL-4B cellsPrimary B cellsBcl-xLCell deathBcl-2 family membersBcl-xL transcriptionB lymphocyte developmentB lymphocyte apoptosisSTAT6-dependent mannerAnti-apoptotic cytokinesActivation of STAT6Splenic B cellsAnti-apoptotic activityIL-4 stimulationInterleukin-4Lymphocyte apoptosisBcl-xL.B lymphocytesMolecular eventsSubsequent transcriptionCytokine receptorsLymphocyte developmentCell survival
2000
Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes*
Fasshauer M, Klein J, Ueki K, Kriauciunas K, Benito M, White M, Kahn C. Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes*. Journal Of Biological Chemistry 2000, 275: 25494-25501. PMID: 10829031, DOI: 10.1074/jbc.m004046200.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose Tissue, BrownAnimalsArabidopsis ProteinsAzo CompoundsBiological TransportCell DifferentiationCell MembraneCells, CulturedColoring AgentsDose-Response Relationship, DrugGlucoseGlucose Transporter Type 4ImmunoblottingInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPlant ProteinsPlasmidsPotassium ChannelsPrecipitin TestsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRetroviridaeSignal TransductionSubcellular FractionsTime FactorsConceptsInsulin-stimulated GLUT4 translocationGLUT4 translocationInsulin-induced glucose uptakeIRS-2Plasma membraneDownstream effectorsWild typeInsulin receptor substrate (IRS) proteinsBrown adipocyte cell lineInsulin stimulationGlycogen synthase kinase-3IRS-2-associated phosphatidylinositolGlucose uptakeAkt-dependent phosphorylationInsulin receptor substrate 2Synthase kinase-3Brown adipocytesMajor downstream effectorActivity of AktMature brown adipocytesAdipocyte cell lineSubstrate proteinsWild-type counterpartsKO cellsKinase 3